The creation of durable, functional and biocompatible implants and sensors is key to improved patient outcomes and lower medical costs. Surface fouling of body-fluid-contacting devices by non-specific protein adsorption and cell attachment, and the consequent surface-induced thrombotic and inflammatory responses, degrade device performance and lead to adverse outcomes that require medical intervention. The extensive literature on surface modifications aimed at preventing bio-fouling highlights both the broad potential and the current limitations of this strategy for improving medical device and health outcomes. Recent reports have demonstrated that certain zwitterionic and ampholytic polymers are effective at inhibiting biofouling. However, a mechanistic understanding of this behavior is lacking. We hypothesize that controlling the spatial separation of oppositely charged groups within a certain length-scale smaller than the size of proteins, while maintaining the zero net charge in a polymer brush, imparts the brush surface with resistance to protein adsorption. Accordingly, this project aims to design and synthesize zero net charge polymer brushes with a range of separation between oppositely charged groups, evaluate their resistance to protein adsorption and cell adhesion, and analyze the pertinent structure-function relationships. The systematic study of the charge separation will be enabled by the solid phase synthesis of peptidomimetic polymers. This technique allows absolute control over monomer sequence, brush length and thus charge separation. This research training will be aided by the multidisciplinary profile of the investigator's research group, consisting of medical students and scientists in cell, chemical and materials engineering. The outcomes of this study will include identification of novel anti-fouling brush surfaces applicable to therapeutic and diagnostic devices, and fundamental knowledge of the configurational requirements for imparting anti-fouling properties to (pseudo)zwitterionic materials. The investigation of polymer systems possessing molecular level, sequence-specific chemical and spatial cues will advance the development of biomaterials that elicit desirable biorecognition properties. PUBLIC HEALTH RELEVANCE: This experimental study will systematically investigate the molecular structure required to confer anti-fouling properties to polymers possessing a balanced number of electrostatic charges. Coating biomedical devices with such anti-fouling polymers would prevent unwanted fouling by biomolecules and cells, which would improve device performance and patient outcomes, and lower medical costs.